Schematic representation of our results. We established 2 types of iPSC lines derived from individual female patients with XLSA harboring the ALAS2-R227C mutation. WT iPSCs showed mature erythroid differentiation, and MT iPSCs stopped at the immature erythroblast stage, recapitulating the pathogenesis of XLSA. AZA administration reactivated the silent WT ALAS2 allele in MT HPCs and ameliorated erythroid differentiation defects. The figure was created using BioRender.com.